DESCRIPTION: The RNA-dependent RNA polymerase of poliovirus has been investigated extensively as one of the few RNA-dependent RNA polymerases that is amenable to biochemical analyses. Dr. Schultz has solved the three-dimensional structure of the poliovirus polymerase at 2.5 Angstrom resolution by x-ray crystallography. Structural analyses will continue with refinement, analysis of other crystal forms, and co-crystallization of the polymerase with primed-template RNAs and NTPs. The structure of the poliovirus polymerase represents the fourth and final class of templete-dependent polymerases; at least one structure for each of the other three classes (DNA-dependent DNA, DNA-dependent RNA, and RNA-dependent DNA) has previously been determined. Structural comparisons of these four classes of polymerases demonstrate that whereas a majority of their structures are quite different, their palm subdomains are closely related. Conserved structural elements in the palm subdomain correspond nicely to the conserved amino acid sequence motifs derived from extensive efforts to align polymerase sequences. Once the structure of the poliovirus polymerase is sufficiently refined, a detailed and thorough analysis of the conserved polymerase sequence/structure motifs will be pursued. Preliminary analyses suggest that several modifications in the current alignments will serve for analyzing the roles of conserved amino acids and as a tool for evaluating polymerases of unknown structure. As one of very few structures of viral replication proteins, the poliovirus polymerase structure has many important implications with regard to viral replication, once the refinement of the poliovirus polymerase structure is completed. The wealth of information available from biochemical and mutational analyses will be carefully evaluated. In addition, Dr. Schultz will explore the intriguing and tremendously important possibility that oligomerization of the poliovirus polymerase is critical for its function and that extensive polymerase-polymerase interactions observed in the crystals might provide structural models for this oligomerization.